Safety and Efficacy Study of Daptomycin in Pediatric Participants (1 to 17 Years-old) With Skin and Skin Structure Infections

This study has been completed.

Sponsor:

Cubist Pharmaceuticals LLC

ClinicalTrials.gov Identifier:

NCT00711802

First Posted: July 9, 2008

Last Update Posted: June 20, 2017

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This is a multi-center, evaluator-blinded, randomized, comparative study designed to assess the safety, efficacy, and pharmacokinetics (PK) of daptomycin in pediatric subjects ages 1 to 17 years, inclusive, with complicated skin and skin structure infections (cSSSI) caused by Gram-positive pathogens.

An Evaluation of the Safety, Efficacy and Pharmacokinetics of Daptomycin in Pediatric Subjects Aged One to Seventeen Years With Complicated Skin and Skin Structure Infections Caused by Gram-Positive Pathogens

Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Baseline through 14 days after last dose of study drug ]

A TEAE was defined as any treatment-emergent adverse event (AE) that occurred from the time of first dose of the study drug through the last study evaluation or pre-existing adverse AEs that were aggravated in severity or frequency during the dosing period. The percentage of participants with at least 1 TEAE, with at least one drug-related AE (drug-related included "possibly related" or "related" as deemed by the Investigator; it also included events if causality was missing), and who discontinued from treatment due to a TEAE is presented. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

Secondary Outcome Measures:

Percentage of Participants With an Overall Therapeutic Response at Test of Cure Visit [ Time Frame: Baseline through 14 days after last dose of study drug ]

The assessment of therapeutic response was determined by comparing a participant's signs and symptoms at the test of cure visit (up to 14 days after last dose) to those recorded at baseline. Participants were classified as "Success" or "Failure" by combining their clinical and microbiological efficacy responses. Resolution of clinically significant signs and symptoms associated with the skin infection present at study baseline was considered "Success" by the Investigator. These participants were deemed both clinically cured and microbiologically eradicated. For participants whose clinical course could not be clearly defined as improved, a clinical outcome of "Failure" was rendered. In addition, if it was determined that the primary site of infection required additional antibiotic treatment, the assessment of clinical response was "Failure." If the Investigator was unable to determine a response because the participant was lost to follow-up, the assessment was "Unable to evaluate."

Pharmacokinetics (PK): Area Under the Plasma Concentration-Time Curve for Daptomycin From 0 to the Last Sampling Time Point (AUC[0-t]) [ Time Frame: Predose and 5 timepoints according to age group (up to 12 hours postdose) ]

Participants who volunteered for PK sampling had a blood sample collected for analysis at the following time points:

Administered intravenously (IV) every 24 hours for up to 14 days at the following age-dependent dosages.

Participants ages 7 to 17 years: daptomycin was dissolved in a volume of 50 milliliters (mL) 0.9% sodium chloride for injection over 30 minutes (min) with an infusion rate of 1.67 mL/min.

Participants 1 to 6 years-old: daptomycin was dissolved in a volume of 25 mL 0.9% sodium chloride for injection over 60 min with an infusion rate was 0.42 mL/min.

Age Group 1 (for ages 12 to 17 years): 5 milligrams/kilogram (mg/kg)

Age Group 2 (for ages 7 to 11 years): 7 mg/kg

Age Group 3 (for ages 2 to 6 years): 9 mg/kg

Age Group 4 (for ages 1 to <2 years): 10 mg/kg

Drug: Daptomycin

Other Name: Cubicin

Active Comparator: Standard of Care (SOC)

The comparator agent for this study was the SOC treatment and dosage deemed appropriate by the Investigator. The recommended SOC agents were IV vancomycin, IV clindamycin, and IV semisynthetic penicillins every 24 hours for up to 14 days.

Drug: Standard of Care (SOC)

Other Name: nafcillin, oxacillin, cloxacillin

Detailed Description:

This is a multi-center, evaluator-blinded, randomized, comparative study designed to assess the safety, efficacy, and PK of daptomycin in pediatric participants ages 1 to 17 years, inclusive, with cSSSI caused by Gram-positive pathogens. Participants will be enrolled into age groups and given age-dependent doses over a period of up to 14 days. Participants will be stratified by age group to receive either daptomycin or SOC (recommended as vancomycin, clindamycin or semisynthetic penicillin) in a ratio of 2:1, respectively. Participants may continue on oral therapy following completion of IV study drug administration and provided that the participant meets all criteria for conversion to oral therapy, including clear clinical improvement and availability of an oral agent to which the pathogen is susceptible. The choice of oral therapy will be left to the discretion of the Investigator. February 11, 2015 released from post marketing requirement to include subjects aged 3 months - < 1 year. Ref ID: 3701325

Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:

1 Year to 17 Years (Child)

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Written parental (or appropriate legal representative) informed consent prior to any study-related procedure not part of normal medical care

Written participant assent (as appropriate)

Male or female between the ages of 1 and 17 years old, inclusive

If female of childbearing potential (defined as post-menarche), not lactating or pregnant, documented negative pregnancy test result within 48 hours prior to study medication administration and willing to practice reliable birth control measures (at the discretion of the Principal Investigator) during study treatment and for at least 28 days after study completion

Able to comply with the protocol for the duration of the study

Skin and skin structure infections of a complicated nature known or suspected to be caused by Gram-positive pathogen(s) that require IV antibiotic treatment. Complicated infections are defined as infections either involving deep soft tissue or requiring significant surgical intervention (such as, infected ulcers, burns, and major abscesses) or infections in which the participant has a significant underlying disease state that complicates the response to treatment. The Investigator may contact the Medical Monitor to discuss infections not meeting this definition but which otherwise appear appropriate for inclusion

Investigational drug use (including daptomycin) or participation in any experimental procedure in the 30 days preceding study entry

Known allergy/hypersensitivity to daptomycin

Known infection caused solely by Gram-negative pathogen(s), fungus(i), or virus(es)

Previous systemic antimicrobial therapy exceeding 24 hours in duration administered anytime during the 48 hours prior to the first dose of study drug (exception: a participant is eligible if on previous antibiotics without any clinical improvement and/or a wound culture is available and the pathogen is not sensitive to prior therapy)

Known or suspected pneumonia, osteomyelitis, meningitis, or endocarditis

Known bacteremia (exception: any participant enrolled in the study that is subsequently found to have a blood culture positive for bacteremia may be continued)

Participant with current or known clinically significant abnormal laboratory test results (including electrocardiograms [ECGs]) that would expose the participant to unacceptable risk as determined by Investigator

History of clinically significant cardiovascular, renal, hepatic, pulmonary (well-controlled asthma is acceptable), gastrointestinal, endocrine, hematological, autoimmune disease, or primary immune deficiency (unless the Investigator considers that the subject would not be at risk by participating in the study [Note: human immunodeficiency virus-infected participants must not be enrolled])

History of or current clinically significant (at the discretion of the Investigator) muscular disease, nervous system, or seizure disorder